Abstracts of Staff Publications
aSpring 2000
A randomized clinical trial to reduce asthma morbidity
among inner-city children: Results of the National Cooperative Inner-City Asthma Study
Richard Evans III, Peter Gergen, Herman Michell, Meyer Kattan, Carolyn Kercsmar, Ellen Crain, et al
From Children’s Memorial Hospital, Chicago; National Institute of Allergy and Infectious Disease; Rho, Inc, Chapel Hill, North Carolina; Mount Sinai School of Medicine, New York; Case Western Reserve University, Cleveland, Ohio; Albert Einstein College of Medicine,
New York; et al.
Journal of Pediatrics 1999;135:332–8
Objective: To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma.
Study design: Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family’s individual asthma risk profile assessed at baseline.
Results: Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06
symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P = .071). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14.8%), a decrease of 4.19% (CI, -8.75 to 0.36, P = .071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor.
Conclusions: We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can deduce asthma symptoms among children in the inner city.
‘Off-label’ use of drugs in pediatric anesthesia:
Legal, clinical and policy considerations
Charles Coté
From the Department of Pediatric Anesthesiology, Children’s Memorial Hospital, Chicago and the Department of Anesthesiology and Pediatrics, Northwestern University Medical School.
Current Opinion in Anaesthesiology 1999;12:325–327
Most drugs used in the care of children have never had appropriate studies conducted by the manufacturer which fulfill Food and Drug Administration requirements necessary to be included in the ‘indications’ portion of the package insert. Any use not described in the indications of the package insert is considered ‘off-label’. A number of editorials and hard work by many individuals have all resulted in new legislation that hopefully will start to make the necessary changes in drug development.
The most important point in all of this discussion is that the clinician must never lose sight of the final paragraph of the Committee on Drugs statement: ‘Lack of approval for a specific use should not prevent physicians from prescribing an available drug in the best interest of their patients.’ It is an ethical obligation of the pharmaceutical industry to perform pediatric studies, because it is a child’s and infant’s right to reap the benefits and advantages of new medications. Children should not continue to be therapeutic orphans. It is clear that this issue is not limited to the United States, but is a world-wide issue.
Management of congenital subglottic hemangioma
C. Anthony Hughes, Ali Rezaee, Jeffrey Ludemann, and Lauren Holinger
From the Division of Pediatric Otolaryngology, Children’s Memorial Hospital; and the Department of Otolaryngology—Head and Neck Surgery, Northwestern University Medical School, Chicago.
Journal of Otolaryngology 1999;28:223–228
Objective: This study was conducted to assess the safety and effi-cacy of individualized management of congenital subglottic hemangioma (CSH) at Children’s Memorial Hospital in Chicago; describe treatment modalities, including endoscopic excision with the carbon dioxide (CO2) laser, systemic corticosteroids, and intralesional corticosteroid injection with short-term intubation; and determine success of these various strategies in avoiding tracheotomy.
Methods: During the 10-year period between January 1, 1988 and December 31, 1997, 28 infants were diagnosed with CSH. A retrospective review of medical records was undertaken to determine demographics, presenting symptoms, location of the lesion, therapeutic modality, and complications. All patients were contacted at the time of writing.
Results: Twenty-eight patients net the criteria for this study. Gender distribution was 1.8:1 female to male. Age at diagnosis ranged from 4 weeks to 8 months, with a mean of 78.8 days and a median of 60 days. The location of CSH was most often posterior and on the left. Associated hemangiomas were found in 14 (50%) cases. The most common symptoms were stridor and cough. Management included 1 to 13 operative direct laryngoscopies and bronchoscopies, endoscopic excision with the CO2 laser, and the use of systemic and intralesional corticosteroids. No patient required tracheotomy.
Conclusion: Morbidity and the need for tracheotomy in CSH patients can be minimized using a combination of therapeutic modalities. Each infant’s treatment is individualized based on the severity of the patient’s symptoms and the morphology of the lesion.
Hematopoietic stem-cell transplantation using unrelated cord-blood versus matched sibling marrow in pediatric bone marrow failure syndrome: One center’s experience
Peter Shaw, Paul Haut, Marie Olszewski, Morris Kletzel
From the Division of Hematology/Oncology, Children’s Memorial Hospital, Chicago
Hematopoietic stem-cell transplantation (HSCT) is an effective mode of therapy in pediatrics for the treatment of both malignant and non-malignant disorders. We compared the course of children transplanted with unrelated umbilical cord blood (UCB) to those transplanted with allogeneic sibling bone marrow (BM) for bone marrow failure syndromes. Thirteen patients with a median age of 6.3 years were transplanted for the following diseases between April 1992 and November 1997: myelodysplastic syndromes, aplastic anemia, Diamond-Blackfan anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, osteopetrosis and dyskeratosis congenita. The stem cell source was BM in ten patients and UCB in three. We
retrospectively examined the conditioning regimens, stem cell source and dose, days to engraftment, survival and complication rate to see whether there was a significant advantage in using one source over the other. The median time to an absolute neutrophil count > 500 per :L was 25 days for UCB patients and 16 days for BM patients. The median time to a platelet count > 20,000 per :L was 55 days for UCB patients and 22 days for BM patients. The 100-day mortality was 66% in UCB patients and 20% in BM patients. The overall mortality rates were 66% and 40% respectively. Three patients died prior to engraftment. Seven patients (54%) were still alive as of May 1999 with a median follow-up of 1574 days post-transplant. The patients transplanted with BM had faster engraftment and lower rates of graft-versus host disease, 100-day mortality and overall mortality. HLA-matched sibling BM is preferred as a source but transplantation using unrelated UCB is still an option in treating pediatric bone marrow failure syndromes.
Posterior spinal fusion and instrumentation for adolescent idiopathic scoliosis: Current techniques and controversies
David Godfried and John Sarwark
From the Division of Orthopedics at Children’s Memorial Hospital
and Northwestern University Medical School, Chicago.
Seminars in Spine Surgery 1998;10:17–22
Posterior spinal fusion with instrumentation has been the widely accepted method of orthopaedic surgical treatment of adolescent idiopathic scoliosis for over 30 years. A clearer understanding of the three-dimensional pathoanatomy and advance in operative technique and instrumentation have continued to improve outcomes. Present day surgical treatment of severe idiopathic scoliosis is a safe and effective method of restoring spinal balance, reducing deformity, and preventing progression. This review discusses the surgical treatment of adolescent scoliosis, focusing on current techniques and controversies.
Dobutamine stress echocardiography:
Experience in pediatric heart transplant recipients
Elfriede Pahl, Susan Crawford, Jeanine Swenson, E. Elise Duffy, F. Jay Fricker, Carl Backer, Constantine Mavroudis, and Farooq Chaudhry
From Children’s Memorial Hospital (Pediatrics, Pathology, Medicine and Surgery) and Northwestern University Medical School, Chicago; and the Department of Pediatrics, University of Pittsburgh School of Medicine.
Journal of Heart and Lung Transplantation 1999;18:725–732
Background: Transplant coronary arteriography causes late death and is difficult to detect noninvasively. Dobutamine stress echocardiography is being used for risk stratefication in adult recipients at some transplant centers, thus we investigated its role in a pediatric population.
Methods: We performed 46 stress echo studies (mean age=11.8 years; mean years post transplantation=4.3). An atropine/dobutamine protocol (5–40mcg/kg/min) was used to attain a predicted target heart rate. Serial echocardiographic images were acquired at baseline and at each increment of dobutamine and recovery, and were digitized online. Data were correlated with endomyocardial biopsy (n=23), coronary angiography (n=26) or autopsy (n=6).
All studies were well tolerated.
Results: Target heartrate was achieved in 41/46 (89%) studies. The mean heartrate significantly increased from 95 to 169 beats/min and mean systolic blood pressure from 123 to 153 mmHg (p <.05). The mean peak pressure-rate product was 23,041 beats-mmHg/min. Coronary arteriography was confirmed in 5 patients by angiography (n=3), explanted heart (n=1) or autopsy (n=4). In this group, abnormalities included a new reversible wall motion abnormality (n=2), left ventricular cavity dilation with stress (n=3), ischemia (n=2), increased mitral insufficiency (n=1) and marked diastolic dysfunction (n=1). A positive study predicted death of graft failure (p <.0005).
Conclusions: Echocardiographic abnormalities during stress correlated with coronary arteriopathy in this small cohort of patients; however, lager multicenter studies are warranted to asses the utility of dobutamine stress echocardiography for risk stratification for coronary disease in pediatric transplant recipients.
Captopril and platelet-activating factor (PAF) antagonist prevent cardiac allograft vasculopathy in rats: Role of endogenous PAF and PAF-like compounds
Susan Crawford, Lijun Huang, Wei Hsueh, Hiroshi Takami,
Frank Gonzalez-Crussi, Carl Backer, Yan Mu, Hanping Liu, and Constantine Mavroudis
From the Department of Pathology and Division of Cardiovascular-Thoracic Surgery, Children’s Memorial Hospital, Northwestern University Medical School, Chicago.
Journal of Heart and Lung Transplantation 1999;18:470–477
Accelerated coronary artery disease (CAD) is the leading cause of late mortality following cardiac transplantation. The vascular lesions are characterized by myointimal proliferation and perivascular mononunclear inflammatory infiltrates. Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator produced by inflammatory cells and activated endothelial cells. Angiotensin II is known to activate phospholipase A2, a critical enzyme in PAF synthesis. Using a rat heterotopic cardiac transplant model known to induce graft CAD, we previously reported that chronic administration of captopril, an angiotensin converting enzyme inhibitor, reduces intimal proliferation and maintains luminal patency. The purpose of the current study was to determine if captopril regulates vascular remodeling by suppressing PAF synthesis and whether administration of a PAF antigonist ameliorates graft CAD. Captopril was found to decrease levels of PAF and PAF-like compounds as well as reduce intimal lesions, decrease cellular rejection grade, and diminish allograft heart weights. Treatment with a PAF antagonist significantly decreased proliferation of the intimal component of the vasculopathy and caused regression of the cardiac hypertrophy, but had no significant effect on cellular rejection. In contrast, untreated animals had elevated plasma PAF levels, elevated heart weights, and severe myointimal proliferation with luminal stenosis 21 days post-transplantation. These observations suggest that graft CAD is mediated, in part, by PAF and PAF-like compounds, and suppression of endogenous PAF may prevent cardiac allograft vasculopathy.
